NPASS Compound

Structure

NPC469580 OpenBabel07101719132D 27 28 0 0 1 0 0 0 0 0999 V2000 -1.7424 -2.1566 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3660 -1.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3660 -1.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8637 0.4824 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1305 1.9914 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6730 1.4483 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1907 -0.4836 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7765 -1.8978 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9659 0.7412 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2247 -0.2247 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6390 1.1895 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8978 0.2235 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -3.3461 1.8966 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -3.6049 -0.4836 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -0.0694 -2.6049 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 2.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5176 -0.9319 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 2.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 10 1 0 0 0 0 2 11 1 0 0 0 0 3 17 1 0 0 0 0 4 17 1 0 0 0 0 7 15 1 0 0 0 0 8 14 1 0 0 0 0 8 16 1 0 0 0 0 9 13 1 0 0 0 0 9 18 1 0 0 0 0 10 23 2 0 0 0 0 10 25 1 0 0 0 0 11 24 2 0 0 0 0 11 26 1 0 0 0 0 12 7 1 6 0 0 0 12 13 1 0 0 0 0 12 19 1 0 0 0 0 13 25 1 1 0 0 0 14 17 1 0 0 0 0 14 20 1 6 0 0 0 15 18 1 6 0 0 0 15 21 1 0 0 0 0 16 19 1 1 0 0 0 16 26 1 0 0 0 0 17 27 1 0 0 0 0 18 5 1 6 0 0 0 18 22 1 0 0 0 0 19 6 1 6 0 0 0 19 27 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	530.01
Volume:	412.524
LogP:	4.786
LogD:	3.71
LogS:	-4.402
# Rotatable Bonds:	5
TPSA:	61.83
# H-Bond Aceptor:	5
# H-Bond Donor:	0
# Rings:	2
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.388
Synthetic Accessibility Score:	4.963
Fsp3:	0.895
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.653
MDCK Permeability:	4.838337918044999e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.051
20% Bioavailability (F20%):	0.189
30% Bioavailability (F30%):	0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.905
Plasma Protein Binding (PPB):	87.04898834228516%
Volume Distribution (VD):	2.013
Pgp-substrate:	17.830764770507812%

ADMET: Metabolism

CYP1A2-inhibitor:	0.074
CYP1A2-substrate:	0.103
CYP2C19-inhibitor:	0.072
CYP2C19-substrate:	0.8
CYP2C9-inhibitor:	0.833
CYP2C9-substrate:	0.049
CYP2D6-inhibitor:	0.007
CYP2D6-substrate:	0.157
CYP3A4-inhibitor:	0.664
CYP3A4-substrate:	0.892

ADMET: Excretion

Clearance (CL):	2.743
Half-life (T1/2):	0.249

ADMET: Toxicity

hERG Blockers:	0.179
Human Hepatotoxicity (H-HT):	0.7
Drug-inuced Liver Injury (DILI):	0.916
AMES Toxicity:	0.534
Rat Oral Acute Toxicity:	0.438
Maximum Recommended Daily Dose:	0.625
Skin Sensitization:	0.874
Carcinogencity:	0.481
Eye Corrosion:	0.977
Eye Irritation:	0.559
Respiratory Toxicity:	0.981

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC469580

Natural Product ID:	NPC469580
*Common Name:**	(5S)-5-Acetoxyacetylcaespitol
IUPAC Name:	[(2S,3S,5S)-2-[(1S,2S,4R,5R)-2-acetyloxy-5-bromo-4-chloro-4-methylcyclohexyl]-5-bromo-2,6,6-trimethyloxan-3-yl] acetate
Synonyms:	(5S)-5-Acetoxyacetylcaespitol
Standard InCHIKey:	OMBBHMVIDWGJKW-NPFZYRJPSA-N
Standard InCHI:	InChI=1S/C19H29Br2ClO5/c1-10(23)25-13-9-18(5,22)15(21)7-12(13)19(6)16(26-11(2)24)8-14(20)17(3,4)27-19/h12-16H,7-9H2,1-6H3/t12-,13-,14-,15+,16-,18+,19-/m0/s1
SMILES:	CC(=O)OC1CC(C(OC1(C)C2CC(C(CC2OC(=O)C)(C)Cl)Br)(C)C)Br
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1088317
PubChem CID:	46881053
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000267] Organohalogen compounds [CHEMONTID:0002867] Alkyl halides [CHEMONTID:0004485] Cyclohexyl halides

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO29486	Laurencia catarinensis	Species	Rhodomelaceae	Eukaryota	n.a.	Brazilian	n.a.	PMID[20039643]
NPO29486	Laurencia catarinensis	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	3

Activity Type	# Activity
Cell Line	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT139	Cell Line	HT-29	Homo sapiens	IC50	>	100000.0	nM	PMID[512940]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	>	100000.0	nM	PMID[512940]
NPT762	Cell Line	A-431	Homo sapiens	IC50	>	100000.0	nM	PMID[512940]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC469580 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	448
0.1-0.2	5309
0.2-0.3	19027
0.3-0.4	9833
0.4-0.5	7492
0.5-0.6	557
0.6-0.7	20
0.7-0.8	5
0.8-0.85	0
0.85-0.9	0
0.9-0.95	5
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9487	High Similarity	NPC469556
0.9459	High Similarity	NPC469581
0.9367	High Similarity	NPC469555
0.9189	High Similarity	NPC277993
0.9189	High Similarity	NPC33876
0.7848	Intermediate Similarity	NPC83368
0.7432	Intermediate Similarity	NPC308569
0.7432	Intermediate Similarity	NPC469572
0.7432	Intermediate Similarity	NPC469582
0.7024	Intermediate Similarity	NPC150938
0.6633	Remote Similarity	NPC475934
0.6596	Remote Similarity	NPC76909
0.6588	Remote Similarity	NPC123122
0.6582	Remote Similarity	NPC469573
0.6522	Remote Similarity	NPC282598
0.6506	Remote Similarity	NPC475786
0.6351	Remote Similarity	NPC291724
0.6351	Remote Similarity	NPC274261
0.6277	Remote Similarity	NPC93616
0.625	Remote Similarity	NPC204173
0.6211	Remote Similarity	NPC279260
0.6211	Remote Similarity	NPC246347
0.6207	Remote Similarity	NPC476718
0.6146	Remote Similarity	NPC471377
0.6136	Remote Similarity	NPC475793
0.6136	Remote Similarity	NPC237510
0.6111	Remote Similarity	NPC244002
0.6	Remote Similarity	NPC476928
0.6	Remote Similarity	NPC136424
0.5955	Remote Similarity	NPC472945
0.5955	Remote Similarity	NPC472944
0.5934	Remote Similarity	NPC476719
0.5926	Remote Similarity	NPC185116
0.5914	Remote Similarity	NPC472951
0.5914	Remote Similarity	NPC471216
0.5914	Remote Similarity	NPC15714
0.5914	Remote Similarity	NPC472943
0.5914	Remote Similarity	NPC471217
0.587	Remote Similarity	NPC43463
0.587	Remote Similarity	NPC252483
0.587	Remote Similarity	NPC191345
0.5851	Remote Similarity	NPC470154
0.5851	Remote Similarity	NPC470156
0.5851	Remote Similarity	NPC71541
0.5843	Remote Similarity	NPC109510
0.5806	Remote Similarity	NPC83436
0.5806	Remote Similarity	NPC477287
0.5789	Remote Similarity	NPC477446
0.5789	Remote Similarity	NPC470155
0.5789	Remote Similarity	NPC477447
0.5789	Remote Similarity	NPC477284
0.5778	Remote Similarity	NPC166250
0.5773	Remote Similarity	NPC48210
0.5773	Remote Similarity	NPC469570
0.5745	Remote Similarity	NPC186594
0.573	Remote Similarity	NPC470173
0.5714	Remote Similarity	NPC475276
0.5714	Remote Similarity	NPC471410
0.5714	Remote Similarity	NPC471411
0.5684	Remote Similarity	NPC211049
0.5684	Remote Similarity	NPC119922
0.5684	Remote Similarity	NPC116320
0.5682	Remote Similarity	NPC253123
0.567	Remote Similarity	NPC18953
0.567	Remote Similarity	NPC65133
0.5667	Remote Similarity	NPC474755
0.5667	Remote Similarity	NPC470526
0.5667	Remote Similarity	NPC476422
0.5663	Remote Similarity	NPC472021
0.5652	Remote Similarity	NPC30575
0.5638	Remote Similarity	NPC329871
0.5632	Remote Similarity	NPC179823
0.5625	Remote Similarity	NPC154043
0.5625	Remote Similarity	NPC202688
0.5625	Remote Similarity	NPC286719
0.5625	Remote Similarity	NPC477286
0.5625	Remote Similarity	NPC60018
0.5625	Remote Similarity	NPC216800
0.5618	Remote Similarity	NPC5209
0.5618	Remote Similarity	NPC51956
0.5618	Remote Similarity	NPC29005
0.561	Remote Similarity	NPC240206
0.5604	Remote Similarity	NPC74639
0.5604	Remote Similarity	NPC55508
0.56	Remote Similarity	NPC475817

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC469580 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	485
0.1-0.2	4708
0.2-0.3	3024
0.3-0.4	643
0.4-0.5	273
0.5-0.6	17
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5833	Remote Similarity	NPD371	Approved
0.5618	Remote Similarity	NPD2687	Approved
0.5618	Remote Similarity	NPD2686	Approved
0.5618	Remote Similarity	NPD2254	Approved

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data